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Sci Rep. 2015 Jun 2;5:10833. doi: 10.1038/srep10833.

CRISPR/Cas9 cleavage of viral DNA efficiently suppresses hepatitis B virus.

Author information

1
Department of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
2
Laboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, New York, NY 10065, USA.
3
1] Department of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA [2] Broad Institute, Cambridge, MA 02139, USA [3] Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139.
4
1] Department of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA [2] Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA [3] Division of Gastroenterology and Hepatology, Weill Cornell Medical College, New York, NY 10065, USA.
5
1] Broad Institute, Cambridge, MA 02139, USA [2] McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139.
6
1] Department of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA [2] Broad Institute, Cambridge, MA 02139, USA [3] Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139 [4] McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139.
7
1] Department of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA [2] Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA [3] Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA [4] Broad Institute, Cambridge, MA 02139, USA [5] Howard Hughes Medical Institute, Cambridge, MA 02139, USA [6] Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

Abstract

Chronic hepatitis B virus (HBV) infection is prevalent, deadly, and seldom cured due to the persistence of viral episomal DNA (cccDNA) in infected cells. Newly developed genome engineering tools may offer the ability to directly cleave viral DNA, thereby promoting viral clearance. Here, we show that the CRISPR/Cas9 system can specifically target and cleave conserved regions in the HBV genome, resulting in robust suppression of viral gene expression and replication. Upon sustained expression of Cas9 and appropriately chosen guide RNAs, we demonstrate cleavage of cccDNA by Cas9 and a dramatic reduction in both cccDNA and other parameters of viral gene expression and replication. Thus, we show that directly targeting viral episomal DNA is a novel therapeutic approach to control the virus and possibly cure patients.

PMID:
26035283
PMCID:
PMC4649911
DOI:
10.1038/srep10833
[Indexed for MEDLINE]
Free PMC Article

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